Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed By Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00003196
First received: November 1, 1999
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

It is known that immune reactions of the donor cells against cancer contribute significantly to the ability to achieve cure after bone marrow transplant (BMT). This research study will test an approach to treating cancer that uses immune cells from the donor to fight the cancer cells. The main reason for using this treatment is the evidence that strong immune responses can occur from donor cells and remissions from cancer have been reported in patients whose cancer came back after a bone marrow transplant. This type of treatment is called a donor leukocyte infusion or DLI. It has been shown that it is possible to get complete remissions of the cancer by using DLI. Most success with the use of DLI has been in a form of leukemia called chronic myeloid leukemia. However, there is good evidence that this effect can occur in other diseases including multiple myeloma, lymphoma, and chronic lymphocytic leukemia. This type of immune response against cancer cells is usually called a graft-versus-leukemia (GVL) effect


Condition Intervention
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Refractory Multiple Myeloma
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Waldenström Macroglobulinemia
Drug: chemotherapy
Radiation: total-body irradiation
Procedure: peripheral blood stem cell transplantation
Drug: cyclosporine
Drug: mycophenolate mofetil
Procedure: allogeneic hematopoietic stem cell transplantation
Biological: therapeutic allogeneic lymphocytes

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Induction Of Mixed Hematopoietic Chimerism In Older Patients With B-Cell Malignancies and in Selected Other Diseases, Using Low Dose TBI , PBSC Infusion And Post-Transplant Immunosuppression With Cyclosporine And Mycophenolate Mofetil to be Followed by Donor Lymphocyte Infusion: A Pilot Study.

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Incidence of GVHD, myelosuppression, and infections [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    At the conclusion of the study, all unexpected toxicities will be summarized and reported.

  • Greater than 10% incidence of treatment-related mortality (TRM) after PBSC infusion, defined as death without evidence of disease progression [ Time Frame: Within 65 days of transplant ] [ Designated as safety issue: Yes ]
  • Greater than 20% incidence of TRM after DLI, defined as death without evidence of disease progression [ Time Frame: Within 12 months of DLI ] [ Designated as safety issue: Yes ]
  • Proportion of patients who successfully achieve mixed chimerism [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The proportion of patients who successfully establish mixed chimerism in each group (patients with NHL, CLL or multiple myeloma vs patients with other malignancies) will be estimated and corresponding confidence intervals will be presented.

  • Proportion of patients with mixed chimerism who successfully achieve full donor chimerism [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The proportion of patients with mixed chimerism who are successfully converted to full donor chimerism in each group (patients with NHL, CLL or multiple myeloma vs patients with other malignancies) will be estimated and corresponding confidence intervals will be presented.


Secondary Outcome Measures:
  • Response of malignancy to DLI [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.

  • Incidence of myelosuppression after initial PBSC transplant [ Time Frame: Up to day 56 ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.

  • Incidence of aplasia after DLI [ Time Frame: Up to day 90 ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.

  • Incidence of grades 2-4 acute GVHD after DLI [ Time Frame: Up to day 90 post-DLI ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.

  • Incidence of grades 2-4 acute GVHD after PBSC infusion [ Time Frame: Up to day 56 ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.

  • Incidence of chronic extensive GVHD after DLI [ Time Frame: Up to 1 year post-DLI ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.

  • Dose of cluster of differentiation (CD)3+ cells required to convert mixed to full lymphoid chimeras [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.

  • Incidence of non-relapse mortality [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.


Estimated Enrollment: 30
Study Start Date: September 1997
Primary Completion Date: April 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (irradiation, transplant, immunosuppression, DLI)

CYTOREDUCTION: If necessary, patients with advanced malignancies undergo cytoreductive chemotherapy to reduce tumor size at discretion of primary physician and study investigators.

CONDITIONING REGIMEN: Patients undergo low-dose total-body irradiation followed by allogeneic PBSC transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 to 0 and then PO BID on days 1-35 with taper to day 56. Patients also receive mycophenolate mofetil PO BID on days 0-27.

POST-TRANSPLANT DLI: Patients with mixed chimerism on day 56 and no evidence of GVHD undergo DLI over 30 minutes on day 65 and may receive up to 3 additional infusions in the absence of GVHD and disease progression or persistence. Patients who have not achieved mixed chimerism at day 56 undergo DLI if complete response is not obtained after a 2 month monitoring period.

Drug: chemotherapy
Undergo cytoreductive chemotherapy
Other Name: chemo
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic PBSC transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Drug: cyclosporine
Given IV or PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSC transplant
Biological: therapeutic allogeneic lymphocytes
Undergo DLI
Other Name: ALLOLYMPH

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine whether mixed hematopoietic chimerism can be safely established using a non-myeloablative conditioning regimen in patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma.

II. To determine whether mixed chimerism, established with non- myeloablative conditioning regimens, can be safely converted to full donor hematopoietic chimerism by infusions of donor lymphocytes (DLI).

OUTLINE:

CYTOREDUCTION: If necessary, patients with advanced malignancies undergo cytoreductive chemotherapy to reduce tumor size at discretion of primary physician and study investigators.

CONDITIONING REGIMEN: Patients undergo low-dose total-body irradiation followed by allogeneic peripheral blood stem cell (PBSC) transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine intravenously (IV) twice daily (BID) on days -1 to 0 and then orally (PO) BID on days 1-35 with taper to day 56. Patients also receive mycophenolate mofetil PO BID on days 0-27.

POST-TRANSPLANT DLI: Patients with mixed chimerism on day 56 and no evidence of graft-vs-host disease (GVHD) undergo DLI over 30 minutes on day 65 and may receive up to 3 additional infusions in the absence of GVHD and disease progression or persistence. Patients who have not achieved mixed chimerism at day 56 undergo DLI if complete response is not obtained after a 2 month monitoring period.

After completion of study treatment, patients are followed up at 4, 6, 12, 18, and 24 months and then annually thereafter.

  Eligibility

Ages Eligible for Study:   50 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged > 49 years and < 66 years with NHL, CLL and multiple myeloma who are not eligible for autologous transplantation or have failed prior autologous transplantation; patients with NHL and CLL must have failed prior therapy with an alkylating agent and/or fludarabine; patients with multiple myeloma must have stage II or III disease and received prior chemotherapy
  • Patients < 50 years of age with NHL, CLL and multiple myeloma at high risk of regimen related toxicity through prior autologous transplant or through pre-existing chronic disease affecting kidneys, liver, lungs, and heart will be considered on a case by case basis and presented to professional clinical counselor (PCC)
  • Patients < 66 years of age with other diseases treatable by allogeneic BMT whom through pre-existing chronic disease affecting kidneys, liver, lungs, and heart are considered to be at high risk for regimen related toxicity using standard high dose regimens; autografting must also be contraindicated in these patients and they must be approved for this protocol by both PCC and by the principle investigator; the following diseases are the likely candidates but other less common diseases may be considered and approved by PCC:

    • Myelodysplastic syndromes
    • Myeloproliferative syndromes
    • Acute leukemia in remission
    • Chronic myelogenous leukemia (CML) in 2nd chronic phase
    • Hodgkin's disease
  • Selected patients with any of the above diagnosis who are (a) older than 65 years and < 75 years with a Karnofsky score > 70 and who, apart from age, fulfill eligibility criteria, or (b) < 66 years but ineligible solely because of renal dysfunction; these patients must be approved for transplant by both PCC and the principal investigator
  • DONOR: Human leukocyte antigen (HLA) genotypically identical sibling
  • DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
  • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)
  • DONOR: Age < 75

Exclusion Criteria:

  • Eligible for autologous transplantation
  • Patients with rapidly progressive high grade NHL
  • History of central nervous system (CNS) involvement with disease
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant
  • Patients with a creatinine clearance < 50 ml/min
  • Cardiac ejection fraction < 40% or cardiac failure requiring therapy
  • Severe defects in pulmonary function testing (defects are currently categorized as mild, moderate and severe) as defined by the pulmonary consultant, or receiving supplementary continuous oxygen
  • Total bilirubin > 2 x the upper limit of normal
  • Serum glutamic pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) 4 x the upper limit of normal
  • Karnofsky score < 50
  • Patients with poorly controlled hypertension
  • DONOR: Identical twin
  • DONOR: Age less than 12 years
  • DONOR: Pregnancy
  • DONOR: Infection with human immunodeficiency virus (HIV)
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness
  • DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for donation as described in the Standard Practice Guidelines
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003196

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Stanford University
Stanford, California, United States, 94305
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Germany
Universitaet Leipzig
Leipzig, Germany, D-04103
Italy
University of Torino
Torino, Italy, 10126
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: David Maloney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00003196     History of Changes
Other Study ID Numbers: 1225.00, NCI-2012-00592
Study First Received: November 1, 1999
Last Updated: April 25, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Follicular
Burkitt Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Leukemia, Lymphoid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Hairy Cell
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Mycosis Fungoides
Lymphoma, T-Cell
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Intraocular Lymphoma
Leukemia, Large Granular Lymphocytic
Immunoblastic Lymphadenopathy
Lymphoma, Extranodal NK-T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma
Leukemia
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on September 16, 2014